Intratumoral CD8+ T cells with a tissue-resident memory phenotype mediate local immunity and immune checkpoint responses in breast cancer

Virassamy, B; Caramia, F; Savas, P; Sant, S; Wang, J; Christo, SN; Byrne, A; Clarke, K; Brown, E; Teo, ZL; von Scheidt, B; Freestone, D; Gandolfo, LC; Weber, K; Teply-Szymanski, J; Li, R; Luen, SJ; Denkert, C; Loibl, S; Lucas, O; Swanton, C; Speed, TP; Darcy, PK; Neeson, PJ; Mackay, LK; Loi, S

Author(s): Virassamy, B; Caramia, F; Savas, P; Sant, S; Wang, J; Christo, SN; Byrne, A; Clarke, K; Brown, E; Teo, ZL; von Scheidt, B; Freestone, D; Gandolfo, LC; Weber, K; Teply-Szymanski, J; Li, R; Luen, SJ; Denkert, C; Loibl, S; Lucas, O; Swanton, C; Speed, TP; Darcy, PK; Neeson, PJ; Mackay, LK; Loi, S;
Details: Publication Year 2023-03-13,Volume 41,Issue #3,Page 585-601.e1-e8
Journal Title: Cancer Cell
Publication Type: Research article
Abstract: CD8(+) tumor-infiltrating lymphocytes with a tissue-resident memory T (T(RM)) cell phenotype are associated with favorable prognosis in patients with triple-negative breast cancer (TNBC). However, the relative contribution of CD8(+) T(RM) cells to anti-tumor immunity and immune checkpoint blockade efficacy in breast cancer remains unknown. Here, we show that intratumoral CD8(+) T cells in murine mammary tumors transcriptionally resemble those from TNBC patients. Phenotypic and transcriptional studies established two intratumoral sub-populations: one more enriched in markers of terminal exhaustion (T(EX)-like) and the other with a bona fide resident phenotype (T(RM)-like). Treatment with anti-PD-1 and anti-CTLA-4 therapy resulted in expansion of these intratumoral populations, with the T(RM)-like subset displaying significantly enhanced cytotoxic capacity. T(RM)-like CD8(+) T cells could also provide local immune protection against tumor rechallenge and a T(RM) gene signature extracted from tumor-free tissue was significantly associated with improved clinical outcomes in TNBC patients treated with checkpoint inhibitors.
Publisher: Cell Press
Keywords: Humans; Animals; Mice; *CD8-Positive T-Lymphocytes; *Triple Negative Breast Neoplasms/drug therapy/genetics; Immunologic Memory; Phenotype; Prognosis; Lymphocytes, Tumor-Infiltrating; Ctla-4; Pd-1; cancer immune surveillance; cancer immunotherapy; immune checkpoint blockade; intratumoral CD8(+) T cells; tissue-resident memory cells; triple-negative breast cancer; tumor immunity; tumor infiltrating lymphocytes
Department(s): Laboratory Research
PubMed ID: 36827978
Publisher's Version: https://doi.org/10.1016/j.ccell.2023.01.004
Open Access at Publisher's Site: https://doi.org/10.1016/j.ccell.2023.01.004
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2023-06-15 07:24:52

Last Modified: 2023-06-15 07:25:48